Longitudinal Network Changes and Phenoconversion Risk in Isolated REM Sleep Behavior Disorder.

Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal syndrome for Parkinson's disease (PD) and related α-synucleinopathies. We conducted a longitudinal imaging study of network changes in iRBD and their relationship to phenoconversion. Expression levels for the PD-related motor and cognitive networks (PDRP and PDCP) were measured at baseline, 2 and 4 years, along with dopamine transporter (DAT) binding. PDRP and PDCP expression increased over time, with higher values in the former network. While abnormal functional connections were identified initially within the PDRP, others bridging the two networks appeared later. A model based on the rates of PDRP progression and putamen dopamine loss predicted phenoconversion within 1.2 years in individuals with iRBD. In aggregate, the data suggest that maladaptive reorganization of brain networks takes place in iRBD years before phenoconversion. Network expression and DAT binding measures can be used together to assess phenoconversion risk in these individuals.

Cerebral Glucose Metabolism Is a Valuable Predictor of Survival in Patients with Lewy Body Diseases.

OBJECTIVE: Patients with Lewy body diseases have an increased risk of dementia, which is a significant predictor for survival. Posterior cortical hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (PET) precedes the development of dementia by years. We therefore examined the prognostic value of cerebral glucose metabolism for survival. METHODS: We enrolled patients diagnosed with Parkinson's disease (PD), Parkinson's disease with dementia, or dementia with Lewy bodies who underwent [18F]fluorodeoxyglucose PET. Regional cerebral metabolism of each patient was analyzed by determining the expression of the PD-related cognitive pattern (Z-score) and by visual PET rating. We analyzed the predictive value of PET for overall survival using Cox regression analyses (age- and sex-corrected) and calculated prognostic indices for the best model. RESULTS: Glucose metabolism was a significant predictor of survival in 259 included patients (n = 118 events; hazard ratio: 1.4 [1.2-1.6] per Z-score; hazard ratio: 1.8 [1.5-2.2] per visual PET rating score; both p < 0.0001). Risk stratification with visual PET rating scores yielded a median survival of 4.8, 6.8, and 12.9 years for patients with severe, moderate, and mild posterior cortical hypometabolism (median survival not reached for normal cortical metabolism). Stratification into 5 groups based on the prognostic index revealed 10-year survival rates of 94.1%, 78.3%, 34.7%, 0.0%, and 0.0%. INTERPRETATION: Regional cerebral glucose metabolism is a significant predictor of survival in Lewy body diseases and may allow an earlier survival prediction than the clinical milestone "dementia." Thus, [18F]fluorodeoxyglucose PET may improve the basis for therapy decisions, especially for invasive therapeutic procedures like deep brain stimulation in Parkinson's disease. ANN NEUROL 2024.

Amelioration activity of the high bioaccessible chrysanthemum (Gongju) phenolics on alcohol-induced oxidative injury in AML-12 cells.

The main bioavailable phenolics from of Gongju (GJ) and their mechanism for hepato-protection remain unclear. To select the GJ phenolics with high bioavailability, chrysanthemum digestion and Caco-2 cells were used and their hepato-protective potential were examined by using AML-12 cells. The digestive recovery and small intestinal transit rate of the main phenolic compounds ranged from 28.52 to 69.53% and 6.57% âˆ¼ 15.50%, respectively. Among them, chlorogenic acid, 3,5-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid, showed higher small intestinal transit rates and digestive recoveries. Furthermore, we found that by increasing intracellular Catalase (CAT) and Superoxide dismutase (SOD) viability and lowering Malondialdehyde (MDA) level (P < 0.05), 3,5-dicaffeoylquinic acid significantly mitigated the oxidative damage of AML-12 liver cells more than the other two phenolics. Our results demonstrated that 3,5-dicaffeoylquninic acid was the primary phenolic compounds in GJ that effectively reduced liver damage, providing a theoretical basis for the development of GJ as a potentially useful resource for hepatoprotective diet.

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: A network imaging marker of the treatment response.

Subthalamic nucleus deep brain stimulation (STN-DBS) alleviates motor symptoms of Parkinson's disease (PD), thereby improving quality of life. However, quantitative brain markers to evaluate DBS responses and select suitable patients for surgery are lacking. Here, we used metabolic brain imaging to identify a reproducible STN-DBS network for which individual expression levels increased with stimulation in proportion to motor benefit. Of note, measurements of network expression from metabolic and BOLD imaging obtained preoperatively predicted motor outcomes determined after DBS surgery. Based on these findings, we computed network expression in 175 PD patients, with time from diagnosis ranging from 0 to 21 years, and used the resulting data to predict the outcome of a potential STN-DBS procedure. While minimal benefit was predicted for patients with early disease, the proportion of potential responders increased after 4 years. Clinically meaningful improvement with stimulation was predicted in 18.9 - 27.3% of patients depending on disease duration.

Blueberry anthocyanin based active intelligent wheat gluten protein films: Preparation, characterization, and applications for shrimp freshness monitoring.

The aim of this study was to prepare active intelligent gluten protein films using wheat gluten protein (WG) and apple pectin (AP) as film-forming matrices, and blueberry anthocyanin extract (BAE) as a natural indicator. SEM and FT-IR analyses demonstrated the successful immobilization of BAE in the film matrix by hydrogen bonding interactions and its compatibility with WG and AP. The resultant WG-AP/BAE indicator films demonstrated notable antioxidant activity, color stability, barrier qualities, pH and ammonia response sensitivity, and mechanical properties. Among them, WG-AP/BAE5 exhibited the best mechanical properties (TS: 0.83 MPa and EB: 242.23%) as well as the lowest WVP (3.92 × 10-8 g.m/m2.Pa.s), and displayed high sensitivity to volatile ammonia. In addition, WG-AP/BAE5 showed a color shift from purplish red to green to yellowish green, demonstrating the monitoring of shrimp freshness in real time. Consequently, this study offers a firm scientific foundation for the development of active intelligent gluten protein films and their use in food freshness assessments.

Association between pre-dementia psychiatric diagnoses and all-cause dementia is independent from polygenic dementia risks in the UK Biobank.

BACKGROUND: Psychiatric disorders have been associated with higher risk for future dementia. Understanding how pre-dementia psychiatric disorders (PDPD) relate to established dementia genetic risks has implications for dementia prevention. METHODS: In this retrospective cohort study, we investigated the relationships between polygenic risk scores for Alzheimer's disease (AD PRS), PDPD, alcohol use disorder (AUD), and subsequent dementia in the UK Biobank (UKB) and tested whether the relationships are consistent with different causal models. FINDINGS: Among 502,408 participants, 9352 had dementia. As expected, AD PRS was associated with greater risk for dementia (odds ratio (OR) 1.62, 95% confidence interval (CI), 1.59-1.65). A total of 94,237 participants had PDPD, of whom 2.6% (n = 2519) developed subsequent dementia, compared to 1.7% (n = 6833) of 407,871 participants without PDPD. Accordingly, PDPD were associated with 73% greater risk of incident dementia (OR 1.73, 1.65-1.83). Among dementia subtypes, the risk increase was 1.5-fold for AD (n = 3365) (OR 1.46, 1.34-1.59) and 2-fold for vascular dementia (VaD, n = 1823) (OR 2.08, 1.87-2.32). Our data indicated that PDPD were neither a dementia prodrome nor a mediator for AD PRS. Shared factors for both PDPD and dementia likely substantially account for the observed association, while a causal role of PDPD in dementia could not be excluded. AUD could be one of the shared causes for PDPD and dementia. INTERPRETATION: Psychiatric diagnoses were associated with subsequent dementia in UKB participants, and the association is orthogonal to established dementia genetic risks. Investigating shared causes for psychiatric disorders and dementia would shed light on this dementia pathway. FUNDING: US NIH (K08AG054727).

Arterial chemotherapy for hepatocellular carcinoma in China: consensus recommendations.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.

Achieving Superior Electromagnetic-Absorbing Performances in the Hexagonal Flake BaFe12O19@PVDF Composites.

Combining magnetic and dielectric materials to form a composite can significantly improve its impedance matching and electromagnetic wave absorption performance. Furthermore, composite materials with a core-shell structure hold promise in meeting the demand for lightweight and highly electromagnetic-absorbing properties. In this study, uniform hexagonal flake barium ferrite (BaFe12O19) was prepared using the hydrothermal method. Subsequently, BaFe12O19@PVDF composites were synthesized by the sol-gel method. By adjusting the mass ratio of BaFe12O19 and PVDF, the shell size of the BaFe12O19@PVDF composite material was controlled, and its electromagnetic absorption performance was enhanced. The shell thickness of BaFe12O19@PVDF is 19.64 nm when the BaFe12O19: PVDF mass ratio is 1:1.0, and the optimal impedance matching is obtained at 13.4 GHz. Meanwhile, at a thickness of 1.5 mm, the minimum reflection loss (RLmin) reached -58.04 dB, and an effective absorption bandwidth (EAB) (RL ≤ -10 dB) of 5.53 GHz was achieved within the frequency range of 11.65 to 15.63 GHz and from 16.36 to 17.91 GHz. Besides, the composites with a matching thickness of 3.5 mm show a maximum EAB of 15.90 GHz when the mass ratio of BaFe12O19 to PVDF is 1:1.2. Within the frequency range of 2-18 GHz, the coverage of reflection loss less than -10 dB is 99.38%, almost achieving full coverage. These results demonstrate that BaFe12O19@PVDF composites exhibit excellent electromagnetic-absorbing performances, making them an excellent candidate for electromagnetic wave absorption in 5G communications.

Liver proteomics analysis reveals the differentiation of lipid mechanism and antioxidant enzyme activity during chicken embryonic development.

Chicken embryo development is a dynamic process. However, no detailed information is available about the protein abundance changes associated with the lipid mechanism and antioxidant enzyme activity during the egg embryo development. Thus, in the present study, an TMT-based proteomic approach was used to quantify protein abundance changes at different stages of chicken embryonic development. A total of 289 significantly differentially abundant hepatic proteins were quantified, of which 180 were upregulated and 109 were downregulated in the comparison of Day 20 with Day 12 in chicken embryos. Pathway analysis showed that metabolic pathways were the most highly enriched pathways, followed by arachidonic acid metabolism and steroid biosynthesis. Integration of proteomic-based studies profiling of three incubation stages revealed that the two compare groups (Day 12 vs Day 20 and Day 16 vs Day 20) shared some key differentially abundant proteins (DAPs), including LBFABP, FABP5, CYP4V2, PDCD4, LAL, APOA1, APOA4, SAA, FABP2, ACBSG2, FABP2, CYP51A1, and FBXO9. The STRING database and GO analysis results showed that there was close connectivity between APOA4, LBFABP, SERPINC1, APOA1, FGB, FGA, ANGPTL3 and these proteins were involved in the oxidation-reduction process, lipid transport, iron ion, heme, and lipid binding. Importantly, APOA4, FABP2, and CYP51A1 might be key factors to control fat deposition and antioxidant enzyme activity during chicken embryonic development. These findings will facilitate a better understanding of antioxidant and lipid mechanisms in chicken embryo and these DAPs can be further investigated as candidate markers to predict lipid deposition and the activity of antioxidant enzymes.

Effect of grape seed proanthocyanidin on the structural and physicochemical properties of bread during bread fermentation stage.

Bread was prepared using wheat flour with grape seed proanthocyanidin (GSP) (0.4%). GSP improved the textural properties of bread including hardness, cohesiviness, gumminess and chewiness. At the last stage of fermentation, GSP reinforced the gluten microstructure with increased the disulfide bonds and hydrophobic interaction and α-helix in the secondary structures. Moreover, GSP addition could increase the total phenolics and antioxidative acitivity of the bread significantly. In addition, the degree of fermentation had a strong influence on the dough forces, and the reasonable control of bread fermentation time was beneficial to improve the bread quality, which provided a reference for the bread processing industry.

A Network Imaging Biomarker of X-Linked Dystonia-Parkinsonism.

OBJECTIVE: The purpose of this study was to characterize a metabolic brain network associated with X-linked dystonia-parkinsonism (XDP). METHODS: Thirty right-handed Filipino men with XDP (age = 44.4 ± 8.5 years) and 30 XDP-causing mutation negative healthy men from the same population (age = 37.4 ± 10.5 years) underwent [18 F]-fluorodeoxyglucose positron emission tomography. Scans were analyzed using spatial covariance mapping to identify a significant XDP-related metabolic pattern (XDPRP). Patients were rated clinically at the time of imaging according to the XDP-Movement Disorder Society of the Philippines (MDSP) scale. RESULTS: We identified a significant XDPRP topography from 15 randomly selected subjects with XDP and 15 control subjects. This pattern was characterized by bilateral metabolic reductions in caudate/putamen, frontal operculum, and cingulate cortex, with relative increases in the bilateral somatosensory cortex and cerebellar vermis. Age-corrected expression of XDPRP was significantly elevated (p < 0.0001) in XDP compared to controls in the derivation set and in the remaining 15 patients (testing set). We validated the XDPRP topography by identifying a similar pattern in the original testing set (r = 0.90, p < 0.0001; voxel-wise correlation between both patterns). Significant correlations between XDPRP expression and clinical ratings for parkinsonism-but not dystonia-were observed in both XDP groups. Further network analysis revealed abnormalities of information transfer through the XDPRP space, with loss of normal connectivity and gain of abnormal functional connections linking network nodes with outside brain regions. INTERPRETATION: XDP is associated with a characteristic metabolic network associated with abnormal functional connectivity among the basal ganglia, thalamus, motor regions, and cerebellum. Clinical signs may relate to faulty information transfer through the network to outside brain regions. ANN NEUROL 2023;94:684-695.

Insight into the phenolics and antioxidant activity of Indian jujube (Ziziphus mauritiana Lamk) peel and pulp subjected to the simulated digestion.

To evaluate the release and activity of Indian jujube phenolics in vivo, its peel and pulp were subjected to simulated digestions. The phenolics content and antioxidant activity of the digested samples were determined. The results showed that the total phenolics/flavonoids in the peel were respectively 4.63 and 4.48 times higher than that in the pulp. The release of phenolics and flavonoids respectively increased by 79.75% and 39.98% in the peel and 86.34% and 23.54% in the pulp after the intestinal digestion. The correlation between the total phenolics/flavonoids and antioxidant activity was higher in the peel (r > 0.858, p < 0.01) than that in the pulp. The phenolics profiles of the peel were almost the same after the digestion, and four phenolics including naringenin tri-glycoside, quercetin-3-O-[(2-hexosyl)-6-rhamnosyl] -hexoside, quercetin-3-O-pentosylhexoside and quercetin-3-O-(2-pentosyl -rhamnoside)-4'-O-rhamnoside were found to be the main flavonoids of Indian jujube peel, and they showed high recovery (>89.88%) during the digestion, implying that these phenolics may play a vital role in the function of Indian jujubes.

The identification and cognitive correlation of perfusion patterns measured with arterial spin labeling MRI in Alzheimer's disease.

BACKGROUND: Vascular dysfunction, including cerebral hypoperfusion, plays an important role in the pathogenesis and progression of Alzheimer's disease (AD), independent of amyloid and tau pathology. We established an AD-related perfusion pattern (ADRP) measured with arterial spin labeling (ASL) MRI using multivariate spatial covariance analysis. METHODS: We obtained multimodal MRI including pseudo-continuous ASL and neurocognitive testing in a total of 55 patients with a diagnosis of mild to moderate AD supported by amyloid PET and 46 normal controls (NCs). An ADRP was established from an identification cohort of 32 patients with AD and 32 NCs using a multivariate analysis method based on scaled subprofile model/principal component analysis, and pattern expression in individual subjects was quantified for both the identification cohort and a validation cohort (23 patients with AD and 14 NCs). Subject expression score of the ADRP was then used to assess diagnostic accuracy and cognitive correlations in AD patients and compared with global and regional cerebral blood flow (CBF) in specific areas identified from voxel-based univariate analysis. RESULTS: The ADRP featured negative loading in the bilateral middle and posterior cingulate and precuneus, inferior parietal lobule, and frontal areas, and positive loading in the right cerebellum and bilateral basal areas. Subject expression score of the ADRP was significantly elevated in AD patients compared with NCs (P < 0.001) and showed good diagnostic accuracy for AD with area under receiver-operator curve of 0.87 [95% CI (0.78-0.96)] in the identification cohort and 0.85 in the validation cohort. Moreover, there were negative correlations between subject expression score and global cognitive function and performance in various cognitive domains in patients with AD. The characteristics of the ADRP topography and subject expression scores were supported by analogous findings obtained with regional CBF. CONCLUSIONS: We have reported a characteristic perfusion pattern associated with AD using ASL MRI. Subject expression score of this spatial covariance pattern is a promising MRI biomarker for the identification and monitoring of AD.

First-Principles Calculations on Narrow-Band Gap d10 Metal Oxides for Photocatalytic H2 Production: Role of Unusual In2+ Cations in Band Engineering.

The d10 metal oxides with low effective mass and high mobility of photoexcited electrons have received much attention in photocatalytic water splitting. However, there are still challenges in practical application due to insufficient visible light absorption. Here, an unusual phenomenon of the In2+ cation in PtIn6(GeO4)2O and PtIn6(Ga/InO4)2 with a narrow band gap is systematically investigated using density functional theory calculations. According to chemical bond analysis, the final band edge structure results from the interaction between the empty In-5p orbitals and the occupied antibonding state of the In 5s-O 2p orbitals as well as the further hybridization of adjacent In cations in PtIn6 octahedrons. The unique bonding characteristic of In2+ cations endows them with a narrow band gap and visible light response ability. Moreover, the occupied antibonding state could weaken the strength of the In-O covalent bond and strengthen the orbital hybridization of the In-In bond, causing the conduction band minimum to be located in the electroactive In6 cavity. This work reveals the origin of the narrow band gap of PtIn6(GeO4)2O and PtIn6(Ga/InO4)2 in view of bond theory and shows that they are promising semiconductors for the application of photocatalytic H2 generation.

A dual tracer [11C]PBR28 and [18F]FDG microPET evaluation of neuroinflammation and brain energy metabolism in murine endotoxemia.

BACKGROUND: Brain metabolic alterations and neuroinflammation have been reported in several peripheral inflammatory conditions and present significant potential for targeting with new diagnostic approaches and treatments. However, non-invasive evaluation of these alterations remains a challenge. METHODS: Here, we studied the utility of a micro positron emission tomography (microPET) dual tracer ([11C]PBR28 - for microglial activation and [18F]FDG for energy metabolism) approach to assess brain dysfunction, including neuroinflammation in murine endotoxemia. MicroPET imaging data were subjected to advanced conjunction and individual analyses, followed by post-hoc analysis. RESULTS: There were significant increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus of C57BL/6 J mice 6 h following LPS (2 mg/kg) intraperitoneal (i.p.) administration compared with saline administration. These results confirmed previous postmortem observations. In addition, patterns of significant simultaneous activation were demonstrated in the hippocampus, the thalamus, and the hypothalamus in parallel with other tracer-specific and region-specific alterations. These changes were observed in the presence of robust systemic inflammatory responses manifested by significantly increased serum cytokine levels. CONCLUSIONS: Together, these findings demonstrate the applicability of [11C]PBR28 - [18F]FDG dual tracer microPET imaging for assessing neuroinflammation and brain metabolic alterations in conditions "classically" characterized by peripheral inflammatory and metabolic pathogenesis.

Effect of Temperature Cycling Pretreatment on the Thermal Stability of Sm2(Co, Fe, Zr, Cu)17 Magnets in the Mild Temperature Range.

The irredeemable magnetic losses of Sm(Co, Fe, Zr, Cu)7.8 permanent magnets caused by oxidation are very important for their practical application. In this work, the simulated results with R2 ≥ 98% based on the data of the temperature cycling test and the long-term isothermal test for the original samples confirmed that the magnetic flux losses reached 9.38% after the 5000th cycle in range R.T.-300 °C, and 7.15% after oxidated at 180 °C for 10 years, respectively. Demagnetization curves showed that the low-temperature oxidation mainly led to the remanence attenuation, while the coercivity remained relatively stable. SEM observation and EDS analysis revealed that an oxide outer layer with a thickness of 1.96 µm was formed on the surface of the original sample at 180 °C for 180 days, in which there was no enrichment or precipitation of metal elements. However, once a Cu, O-rich outer layer with a thickness of 0.72 µm was grown by using a temperature cycling from -50-250 °C for three cycles, the attenuation of magnetic properties could be inhibited under the low-temperature oxidation. This work suggested that the magnetic attenuation of Sm2Co17-type permanent magnets in the low-temperature field could not be ignored, and provided a simple method to suppress this attenuation of magnetic properties below 300 °C.

Profile and activity of phenolic antioxidants in chrysanthemum (Huangshan Gongju) as affected by simulated digestions.

The phenolics are the main bioactive substances of Huangshan Gongju, a famous chrysanthemum of China, but their digestive characteristics are still unknown. To explore the digestive properties of Huangshan Gongju phenolics, the flower was extracted and subjected to simulated digestions, and their phenolic profile and activity were analyzed. The results indicated that the total phenolics content and antioxidant activity of the extract varied with the simulated digestion steps, and they generally decreased in the oral and small intestine digestions but increased in the gastric digestion, and high correlations were detected between the total phenolics content and antioxidant activity (0.873 < r < 0.979, p < .01). The change of phenolic profile during the simulated digestions was similar to that of total phenolics content, and six individual phenolics were identified and quantified, and three of them, including chlorogenic acid, apigenin-7-O-rutinoside, and apigenin-7-O-6″-acetylglucoside showed higher recovery (>64.29%), implying they may be the main functional phenolics of Huangshan Gongju. PRACTICAL APPLICATIONS: This study proved that most phenolics in Huangshan Gongju were relatively stable during digestion. The finding may guarantee the application of Huangshan Gongju in the field of functional foods.

Effects of Wood Flour (WF) Pretreatment and the Addition of a Toughening Agent on the Properties of FDM 3D-Printed WF/Poly(lactic acid) Biocomposites.

In order to improve the properties of wood flour (WF)/poly(lactic acid) (PLA) 3D-printed composites, WF was treated with a silane coupling agent (KH550) and acetic anhydride (Ac2O), respectively. The effects of WF modification and the addition of acrylicester resin (ACR) as a toughening agent on the flowability of WF/PLA composite filament and the mechanical, thermal, dynamic mechanical thermal and water absorption properties of fused deposition modeling (FDM) 3D-printed WF/PLA specimens were investigated. The results indicated that the melt index (MI) of the specimens decreased after WF pretreatment or the addition of ACR, while the die swell ratio increased; KH550-modified WF/PLA had greater tensile strength, tensile modulus and impact strength, while Ac2O-modified WF/PLA had greater tensile modulus, flexural strength, flexural modulus and impact strength than unmodified WF/PLA; after the addition of ACR, all the strengths and moduli of WF/PLA could be improved; after WF pretreatment or the addition of ACR, the thermal decomposition temperature, storage modulus and glass transition temperature of WF/PLA were all increased, and water absorption was reduced.

Evaluation of digestibility differences for apple polyphenolics using in vitro elderly and adult digestion models.

We evaluated the in vitro digestibility of apple polyphenols mimicking elderly and adult digestion models (dynamic and static systems). The digestibility of total apple polyphenols in small intestine was much higher in the adult dynamic system (62 µg/100 g fresh apple) compared to the static system (20 µg/100 g fresh apple) and elderly dynamic digestion conditions (33 µg/100 g fresh apple). Elderly in vitro static digestion showed better antioxidant activity than the adult system (OH and ABTS+ methods). Thus, the in vitro dynamic digestion system can more truly reflect the digestion of apple polyphenols than static digestion system. Moreover, elderly digestion conditions negatively influenced the digestibility of apple polyphenols including chlorogenic acid, epicatechin, phlorizin, rutin, phloretin, hyperoside, proanthocyanidin B2, and quercetin. Hence, appropriate selection of in vitro digestion models for elderly is a prerequisite to exploring the digestibility of phytochemicals for the development of functional food products for elderly.

The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.